thrombolysis treated with tnk-tpa in acute ischemic stroke patients （3t stroke-ii）

Conditions: Acute Ischemic Stroke

Summary: the trial is prospective, block randomized, open-label, blinded endpoint (probe) design. patients with acute ischemic stroke, who are eligible for standard intravenous thrombolysis within 4.5 hours of stroke onset will be randomized 1:1:1 to 0.25mg/kg or 0.40mg/kg intravenous tenecteplase or 0.9 mg/kg alteplase before all participants undergo endovascular thrombectomy.

the study will be a multi-center, prospective, randomized, open- label, blinded endpoint (probe), controlled phase 2 trial (3 arm with 1:1:1 randomization) in ischemic stroke patients. imagine is performed with ct or mri acutely with imaging follow-up at 24-30 hours. the sample size is 225.

Eligibility criteria:
inclusion criteria: * age ≥18 years old; * the clinical diagnosis was acute ischemic stroke the time from onset to treatment was \< 4.5h; the time at which symptoms begin is defined as "the time at which they finally appear normal"; * mrs before onset was ≤1 points; * baseline nihss (at the time of randomization) should be \> 5 and ≤25 points; * informed consent from the patient or surrogate. exclusion criteria: * intracranial hemorrhage identified by ct or mri (cmbs detected by swi is not counted); * massive anterior cerebral infarction identified by ct or mri (aspect \< 6 or lesions larger than one third of the territory of the middle cerebral artery or with a volume larger than 70ml) * a history of severe cns damage (such as aneurysm or arteriovenous malformation, craniocerebral trauma, intracranial or spinal cord surgery) * onset with seizures, and the paralysis was suspected to be related to todd paralysis. * administration of heparin within 48 hours preceding the onset of stroke with a baseline aptt exceeding the upper limit of the normal range. * oral anticoagulant (such as warfarin) treatment with baseline inr\>1.7 or pt\>15 s; * administration of thrombin inhibitors or factor xa inhibitors within 48 hours preceding the onset of stroke with abnormal coagulation parameters or platelet count; * bp couldn't be controlled with aggressive treatment. uncontrolled hypertension was defined as systolic blood pressure \>185 mmhg or diastolic blood pressure \>110 mmhg, measured for three times every 10 minutes. * platelet count of less than 100×109/ l; * blood glucose \ 400 mg/dl (22.22 mmol/l); * history of intracranial hemorrhage or active hemorrhagic disease. (such as gastrointestinal, urinary tract or retinal bleeding) * tumors with an increased risk of bleeding. * prolonged or traumatic cardiopulmonary resuscitation (\>2 min), delivery within the last 10 days or recent puncture of non-compression vessels such as subclavian vein or jugular vein * acute pancreatitis or severe liver disease, including liver failure, cirrhosis, portal hypertension, esophageal varicose veins, and active hepatitis; * aortic arch dissection; * major surgery or severe trauma in the past 2 weeks; * subjects had serious, fatal, or disabling disease with an expected survival of less than 3 months; * unable to complete neurological assessment and follow-up visits because of dementia or mental illness; * pregnant women, lactating women, or have positive pregnancy test; * allergy to tenecteplase or alteplase or their components; * participation in other clinical trials within 3 months prior to screening; * unsuitable to involve in this study or would result in increased risk, as judged by the investigators.

Keywords: tnk-tpa rt-pa acute stroke phase ii trial